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Results for “Cell migration”

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At least 451 records · Page 25Linked to original sources
PubMed2006

Caspase-3-dependent activation of calcium-independent phospholipase A2 enhances cell migration in non-apoptotic ovarian cancer cells.

Calcium-independent phospholipase A(2) (iPLA(2)) plays a pivotal role in phospholipid remodeling and many other biological processes, including inflammation and cancer development. iPLA(2) can be activated by caspase-3 via a proteolytic process in apoptotic cells. In this study we identify novel signaling and functional loops of iPLA(2) activation leading to migration of non-apoptotic human ovarian cancer cells. The extracellular matrix protein, laminin-10/11, but not collagen I, induces integrin- and caspase-3-dependent cleavage and activation of overexpressed and endogenous iPLA(2). The truncated iPLA(2) (amino acids 514-806) generates lysophosphatidic acid and arachidonic acid. Arachidonic acid is important for enhancing cell migration toward laminin-10/11. Lysophosphatidic acid activates Akt that in turn acts in a feedback loop to block the cleavage of poly-(ADP-ribose) polymerase and DNA fragmentation factor as well as prevent apoptosis. By using pharmacological inhibitors, blocking antibodies, and genetic approaches (such as point mutations, dominant negative forms of genes, and siRNAs against specific targets), we show that beta(1), but not beta(4), integrin is involved in iPLA(2) activation and cell migration to laminin-10/11. The role of caspase-3 in iPLA(2) activation and cell migration are supported by several lines of evidence. 1) Point mutation of Asp(513) (a cleavage site of caspase-3 in iPLA(2)) to Ala blocks laminin-10/11-induced cleavage and activation of overexpressed iPLA(2), whereas mutation of Asp(733) to Ala has no such effect, 2) treatment of inhibitors or a small interfering RNA against caspase-3 results in decreased cell migration toward laminin-10/11, and 3) selective caspase-3 inhibitor blocks cleavage of endogenous iPLA(2) induced by laminin-10/11. Importantly, small interfering RNA-mediated down-regulation of endogenous iPLA(2) expression in ovarian carcinoma HEY cells results in decreased migration toward laminin, suggesting that our findings are pathophysiologically important.

Apoptosis↗
PubMed2005

Matrix metalloproteinase-2 contributes to cancer cell migration on collagen.

Matrix metalloproteinases (MMP) are central to tissue penetration by cancer cells, as tumors expand and form metastases, but the mechanism by which MMP-2 contributes to cancer cell migration is not well understood. In the present experiments, both a broad-spectrum MMP inhibitor and the isolated collagen binding domain (CBD) from MMP-2 inhibited cell migration on native type I collagen. These results verified the involvement of MMPs in general and showed that MMP-2, specifically, contributes to cell migration by a mechanism involving MMP-2 interaction with collagen. To exclude potential overlapping effects of MMP-9, additional experiments showed that MMP-2 also contributed to migration of MMP-9-/- cells. To investigate whether the homologous CBD from human fibronectin also inhibited cell migration, we first showed that fragmentation of fibronectin is a feature of breast cancer tumors and that several fragments contained the CBD. However, the recombinant fibronectin domain did not alter cell migration on collagen. This lack of effect on cell migration was explored in competitive protein-protein binding assays, which showed that the affinity of MMP-2 for collagen exceeds that of fibronectin. Furthermore, whereas the isolated MMP-2 CBD inhibited the gelatinolytic activities of MMP-2 and tumor extracts, such an inhibition was not characteristic of the corresponding fibronectin domain. Together, our results provide evidence that MMP-2 is an important determinant of cancer cell behavior but is not inhibited by the collagen binding segment of fibronectin.

Binding Sites↗
PubMedDate not supplied

ECM dependent and integrin mediated tumor cell migration of human glioma and melanoma cell lines under serum-free conditions.

Collagen IV, laminin and fibronectin are constituents of the cerebral extracellular matrix (ECM), which is critical in glioma cell invasion. The aim of the present study was to evaluate the integrin dependent cell-matrix interactions of two tumors with different invasive properties under matrixfree conditions. Two human glioma (GaMG, U373) and melanoma (MV3, BLM) cell lines were grown in serum free medium. Immunofluorescence microscopy of collagen IV, laminin, and fibronectin was performed. The adhesion of monolayer cells and their migration out of multicellular spheroids was quantified for these ECM components. Integrin chains known to act as laminin receptors were blocked by specific antibodies in additional migration assays. All cell lines expressed all the ECM components under serum free conditions. Tumor cell adhesion and migration in both glioma and melanoma cell lines was increased by all the ECM components, laminin being the strongest promotor of migration. However, migration was dose dependent in gliomas, whereas melanomas revealed a dose optimum of 10 micrograms/ml laminin. Antibodies against alpha 3 integrins significantly reduced migration on laminin in all cell lines, anti-beta 1 in all cell lines except U373. Anti-alpha 2 in BLM showed a strong effect, anti-alpha 6 was a stronger inhibitor in glioma than in melanoma cells. Integrins are functionally involved in tumor cell locomotion on laminin. The blocking of laminin related integrin chains markedly reduces cell motility in a varying manner between the cell lines. Moreover, different cell lines utilize different integrins as the laminin receptor.

Cell Adhesion↗
PubMed1997

Cell migration: don't tread on me.

During directed cell migration, telling cells to avoid certain areas may be as important as attracting them to others. The recently identified wunen gene is involved in the repulsive guidance of migrating primordial germ cells in Drosophila.

Animals↗
PubMed2000

Immunohistochemical demonstration of hyaluronan and its possible involvement in axolotl neural crest cell migration.

Hyaluronan (HA), an extracellular matrix component, is involved mainly in the control of cell proliferation, neural crest and tumor cell migration, and wound repair. We investigated the effect of hyaluronan on neural crest (NC) cell migration and its ultrastructural localization in dark (wild-type) and white mutant embryos of the Mexican axolotl (Ambystoma mexicanum, Amphibia). The axolotl system is an accepted model for studying mechanisms of NC cell migration. Using a biotinylated hyaluronan binding protein (HABP), major extracellular matrix (ECM) spaces, including those of NC cell migration, reacted equally positive on cryosections through dark and white embryos. Since neural crest-derived pigment cells migrate only in subepidermal spaces of dark embryos, HA does not seem to influence crest cell migration in vivo. However, when tested on different alternating substrates in vitro, migrating NC cells in dark and white embryos prefer HA to fibronectin. In vivo, such an HA migration stimulating effect might exist as well, but be counteracted to differing degrees in dark and white embryos. The ultrastructural localization of HA was studied by means of transmission electron microscopic immunohistochemistry using HABP and different protocols of standard chemical fixation, cryofixation, embedding, and immunolabeling. The binding reaction of HA to HABP was strong and showed an equal distribution throughout ECM spaces after both standard chemical fixation/freeze substitution and cryofixation. A preference for the somite or subepidermal side was not observed. Following standard fixation/freeze substitution HABP-labeled "honeycomb"-like networks reminiscent of fixation artifacts were more prominent than labeled fibrillar or irregular net-like structures. The latter predominated in adequately frozen specimens following high-pressure freezing/freeze substitution. For this reason fibrillar or irregular net-like structures very likely represent hyaluronan in the complex subepidermal matrix of the axolotl embryo in its native arrangement.

Ambystoma↗
PubMedDate not supplied

Kinetic model for integrin-mediated adhesion release during cell migration.

Under many circumstances, cell migration speed is limited by the rate of cell-substratum detachment at the cell rear. We have constructed a mathematical model to integrate how the biophysical and biochemical interactions between integrins, the cytoskeleton, and the matrix affect rear retraction and linkage dissociation mechanisms. Our model also examines how applied forces and integrin clustering affect retraction kinetics. The model predicts two distinct detachment phenotypes. In the first, detachment is extremely rapid, dominated by integrin extracellular-matrix dissociation, and it occurs at high forces or low adhesiveness. In the second, detachment is much slower, dominated by integrin-cytoskeleton dissociation, and it occurs at low forces or high adhesiveness. The amount of integrin extracted from the rear of the cell is an assay for the detachment phenotype. During rapid detachment cells leave little integrin on the substratum whereas during slow detachment a large fraction of integrin rips from the membrane. This model delineates parameters which can be exploited to regulate cell speed in each detachment regime. The model also offers an explanation as to why some cell types, such as leukocytes or keratocytes, are able to detach easily and move very quickly while other cell types, such as fibroblasts, tend to migrate more slowly and release many more integrins during detachment.

Binding Sites↗
PubMed1983

Calcium dependency of aortic smooth muscle cell migration induced by 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid. Effects of A23187, nicardipine and trifluoperazine.

We have previously reported that 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE), a 12-lipoxygenase product of arachidonic acid in platelets, is a potent chemoattractant for rat aortic smooth muscle cells. In the present study, the mechanism involved in 12-HETE-associated smooth muscle cell migration was investigated in relation to calcium mobilization in the cells. Migration of smooth muscle cells was measured by a filter membrane technique in modified Boyden chambers. Smooth muscle cell migration induced by 12-HETE increased with the increase of extracellular Ca2+ concentration and became maximal at the physiological Ca2+ concentration of 1.25 mM. The calcium ionophore A23187, at concentrations of 0.2 and 2.0 microM, significantly stimulated cell migration. Nicardipine, a potent calcium-entry blocker, significantly inhibited 12-HETE-associated smooth muscle cell migration at concentrations from 10(-9) to 10(-5) M. Concentrations of trifluoperazine from 10(-9) to 10(-5) M and W-7 at 10(-5) M, which are specific inhibitors of calmodulin, also significantly inhibited cell migration induced by 12-HETE. Cytochalasin B at 1.0 and 10 microM, and colchicine at 0.1 and 1.0 microM concentrations drastically inhibited cell migration, indicating that actin-containing microfilaments and microtubules are involved in smooth muscle cell migration. These findings indicated that the stimulation of smooth muscle cell migration by 12-HETE is a highly calcium-dependent process and suggest that 12-HETE might act at the initial stage of smooth muscle cell migration through enhancing calcium influx through plasma membrane and thus stimulating cell migration.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1989

[Use of acridine orange in the estimation of lymphoid cell migration in an organism].

Lymphoid cell migration was studied on the model of their transplantation from animal-donors to recipients. The studied organs were crushed small in the saline solution. The number of nuclei-containing elements has been determined in the obtained suspensions. Smears have been prepared and studied with the help of luminescence microscope combined with phase contrast device. We have determined and counted the ratio of "acridine orange cells" glittering in ultra-violet rays to all visible in phase-contrast nuclei containing cells. Then we have found the percentage of the marked cells in the organ from the total number of the injected lymphocytes. The usage of the given technique shown the enhancement of thymus cell migration to the liver after partial hepatectomy.

Acridine Orange↗
PubMed2005

Cell migration and invasion assays.

The processes of cell migration and invasion are integral to embryonic development and the functioning of adult organisms. Deregulation of these processes contributes to numerous diseases. Ras GTPases and in particular members of the Rho subfamily of GTPases play critical roles in cell migration and invasion. Here, we provide a collection of protocols to assay these functions. We describe two cell migration assays. The monolayer wound healing assay is very easy to implement, whereas the microliter-scale migration assay allows examination of cell behavior on defined extracellular matrices. We also describe two methods that allow the quantification of tumor cell invasion, a versatile transwell Matrigel invasion assay and an organotypic assay that examines the invasion of glioma cells through a rat brain slice.

Animals↗
PubMed2005

Growth factors stimulate kidney proximal tubule cell migration independent of augmented tyrosine phosphorylation of focal adhesion kinase.

Migration of human proximal tubule cells (HKC-5) was stimulated by epidermal growth factor (EGF), hepatocyte growth factor (HGF), and insulin-like growth factor-1 (IGF-1). Integrin signaling via phosphorylation of focal adhesion kinase (FAK) appears to play a central role in cell migration. Once stimulated, FAK undergoes autophosphorylation at tyrosine (Y) 397, followed by phosphorylation of several sites including Y576/Y577 which increases FAK's kinase activity, as well as at Y407, Y861, and Y925. EGF, HGF, and IGF-1 stimulate FAK phosphorylation in various cells. We showed that endothelin stimulated phosphorylation of Y397 in fibroblasts but not HKC-5 cells. After EGF stimulation, HKC-5 cells showed no change in tyrosine phosphorylation at FAK Y397, 407, 576, 861, or 925. Similarly, HGF and IGF-1 did not stimulate the phosphorylation of FAK Y397 in HKC-5 cells. Further, after inhibition of FAK expression by siRNA, cell migration was similar to cells treated with non-target siRNA and responded to EGF with increased migration. Thus, in proximal tubule cells, stimulation of cell migration by growth factors was independent of augmented FAK tyrosine phosphorylation.

3T3 Cells↗
PubMed1981

Kinetic analysis of epithelial cell migration in the mouse descending colon.

The kinetics of epithelial cell replacement in the descending colon of the mouse were studied using cell counts and other measurements in mice given a single injection of 3H-thymidine at 10:00 a.m. Cell migration occurs from the base of the crypts in the direction of the colonic lumen. The mean turnover time of epithelial cells as measured after the single injection of 3H-thymidine has been estimated at 4.85 days. Since this figure is in agreement with published data based on continuous infusion of the labeled precursor, it is concluded that the time selected for the analysis provides an index of proliferation which is representative of the mean proliferative activity of the epithelium. If each side of a crypt cut along its axis is referred to as a "crypt column," the mean number of cells per crypt column has been found to be 32.9; after a one-hour pulse labeling starting at 10:00 a.m., the mean number of labeled cells per column was 2.8; and the overall labeling index of the epithelium, 8.6%. The frequency of labeled cells in each cell position along the crypt column varies according to a Poisson distribution with a peak close to position 3. Presumably then, cell proliferation is taking place in a random manner and is, therefore, asynchronous, despite evidence to the contrary in the literature. The kinetic analysis supports the view that cell migration occurs along the crypt column in the direction of the colonic lumen at a velocity averaging 0.28 cell position per hour, or 4.48 microns per hour. The results support the view that vacuolated-columnar, mucous, and caveolated cells migrate jointly; whereas entero-endocrine cells migrate separately from these cell lines, except during the initial stages of the migration.

Animals↗
PubMed2001

Activated armadillo/beta-catenin does not play a general role in cell migration and process extension in Drosophila.

Human beta-catenin and its fly homolog Armadillo are best known for their roles in cadherin-based cell-cell adhesion and in transduction of Wingless/Wnt signals. It has been hypothesized that beta-catenin may also regulate cell migration and cell shape changes, possibly by regulating the microtubule cytoskeleton via interactions with APC. This hypothesis was based on experiments in which a hyperstable mutant form of beta-catenin was expressed in MDCK cells, where it altered their migratory properties and their ability to send out long cellular processes. We tested the generality of this hypothesis in vivo in Drosophila. We utilized three model systems in which cell migration and/or process extension are known to play key roles during development: the migration of the border cells during oogenesis, the extension of axons in the nervous system, and the migration and cell process extension of tracheal cells. In all cases, cells expressing activated Armadillo were able to migrate and extend cell processes essentially normally. The one alteration from normal involved an apparent cell fate change in certain tracheal cells. These results suggest that only certain cells are affected by activation of Armadillo/beta-catenin, and that Armadillo/beta-catenin does not play a general role in inhibiting cell migration or process extension.

Animals↗
PubMed2005

The roles of two C. elegans HOX co-factor orthologs in cell migration and vulva development.

Anteroposterior cell migration and patterning in C. elegans are governed by multiple, interacting signaling pathways and transcription factors. In this study, we have investigated the role of ceh-20, the C. elegans ortholog of the HOX co-factor Extradenticle (Exd/Pbx), and unc-62, the C. elegans ortholog of Homothorax (Hth/Meis/Prep), in two processes that are regulated by Hox gene lin-39: cell migration and vulva formation. As in lin-39 mutants, the anterior migrations of neuroblasts in the Q lineage are truncated in Hox co-factor mutants. Surprisingly, though, our findings suggested that the roles of ceh-20 and unc-62 are different from that of lin-39; specifically, ceh-20 and unc-62 but not lin-39 are required for the transmembrane protein MIG-13 to promote anterior migration. To our knowledge, ceh-20 and unc-62 are the only genes that have been implicated in the mig-13 pathway. We find that ceh-20 and unc-62 are also required for several steps in vulva development. Surprisingly, ceh-20 and unc-62 mutants have phenotypes that are starkly different from those of lin-39 mutants. Thus, in this process, too, ceh-20 and unc-62 are likely to have functions that are independent of lin-39.

Animals↗
PubMed2004

nm23-H1 reduces in vitro cell migration and the liver metastatic potential of colon cancer cells by regulating myosin light chain phosphorylation.

The nm23-H1 gene is known as a potential metastasis suppressor gene in various types of carcinomas. However, the role of nm23-H1 in colorectal carcinoma still remains controversial and the cellular mechanisms by which its protein may modulate the metastatic phenotype are not yet known. We transfected nm23-H1 cDNA into the human colon cancer cell line, HT-29, to test the effects and cellular biological mechanism of nm23 protein in colon cancer. We found that nm23-H1 strongly inhibited the liver metastasis of HT-29 cells in nude mice and inhibited the epidermal growth factor (EGF)-induced cell migration in vitro. Furthermore, we clarified the regulation of the myosin light chain (MLC) phosphorylation by nm23-H1, which has been demonstrated as having potential role in cell migration.

Animals↗
PubMed1998

Apolipoprotein E inhibits platelet-derived growth factor-induced vascular smooth muscle cell migration and proliferation by suppressing signal transduction and preventing cell entry to G1 phase.

The anti-atherogenic effects of apolipoprotein (apo) E have been attributed to its ability to reduce plasma cholesterol level and to limit foam cell formation. The purpose of this study was to ascertain if apoE also may have cytostatic functions that could attenuate vascular occlusive diseases. Purified apoE inhibited smooth muscle cell migration directed to platelet-derived growth factor (PDGF) or oxidized LDL (oxLDL) (p < 0.0001). The purified apoE also suppressed PDGF- and oxLDL-induced smooth muscle cell proliferation (p < 0.001). These apoE inhibitory effects were not because of suppression of PDGF binding to its receptors on the smooth muscle cells, but was correlated with a significant reduction in agonist-stimulated mitogen-activated protein kinase activity (p < 0.01). ApoE also inhibited PDGF-induced cyclin D1 mRNA expression, suggesting that the apoE effect was mediated by growth arrest at the G0 to G1 phase. Taken together, these results suggest that apoE has cytostatic functions in the vessel wall and may protect against vascular diseases through inhibition of cell signaling events associated with growth factor-induced smooth muscle cell migration and proliferation.

Animals↗
PubMed1991

Primary mesenchyme cell migration requires a chondroitin sulfate/dermatan sulfate proteoglycan.

Primary mesenchyme cell migration in the sea urchin embryo is inhibited by sulfate deprivation and exposure to exogenous beta-D-xylosides, two treatments known to disrupt proteoglycan synthesis. We show that in the developing sea urchin, exogenous xyloside affects the synthesis by the primary mesenchyme cells of a very large, cell surface chondroitin sulfate/dermatan sulfate proteoglycan. This proteoglycan is present in a partially purified fraction that restores migratory ability to defective cells in vitro. The integrity of this chondroitin sulfate/dermatan sulfate proteoglycan appears essential for primary mesenchyme cell migration since treatment of actively migrating cells with chondroitinase ABC reversibly inhibited their migration in vitro.

Animals↗
PubMed2005

Urokinase signal transduction and its role in cell migration.

Urokinase and its receptor uPAR play a role in cell migration that is being actively characterized. We previously reported that urokinase potentiates cell migration in human airway smooth muscle cells only where there is some primary migratory stimulus such as PDGF or recent exposure to growth medium. In this study, we examined the signaling of urokinase through its receptor, which lacks an intracellular domain and is presumed to act through associations with other membrane proteins. Whereas PDGF (30 min) and PDGF with urokinase increased the amount of the tyrosine dephosphorylase SHP2 in the membrane fraction, urokinase alone (30 min) decreased membrane SHP2. Analysis of the time course of urokinase stimulation showed that SHP2 was brought into association with the urokinase receptor uPAR between 2.5 and 20 min of urokinase, and later dissociated from it. Focal adhesion kinase was steadily lost from association with uPAR during urokinase stimulation, but its phosphorylation state increased and it became cleaved to smaller molecules. Association of uPAR with caveolin also decreased during urokinase stimulation. In contrast, the tyrosine kinase Src increased in the membrane fraction in response to urokinase stimulation. Disruption of raft structures by cyclodextrin treatment led to potentiation of PDGF chemotaxis, similar to urokinase action. Blocking of dephosphorylase activity with vanadate reduced basal cell migration and blocked the action of urokinase on PDGF chemotaxis. These observations support a role for urokinase in altering the phosphorylation state of focal adhesions, leading to breakdown of their structure and facilitation of cell motility.-Carlin, S. M., Resink, T. J., Tamm, M., Roth, M. Urokinase signal transduction and its role in cell migration.

Cell Line↗